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Updated: Dec 11, 2025

Measuring G-protein-coupled Receptor Signaling via Radio-labeled GTP Binding
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Measuring G-protein-coupled Receptor Signaling via Radio-labeled GTP Binding

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Structural Basis of the Activation of Heterotrimeric Gs-Protein by Isoproterenol-Bound β1-Adrenergic Receptor

Minfei Su1, Lan Zhu2, Yixiao Zhang3

  • 1Department of Physiology and Biophysics, Weill Cornell Medical College of Cornell University, New York, NY 10065, USA.

Molecular Cell
|August 21, 2020
PubMed

Insights

Researchers uncovered how the beta-1 adrenergic receptor (β1-AR) activates Gs proteins, crucial for heart function. This molecular insight into G-protein-coupled receptor signaling may inform treatments for heart failure.

Area of Science:

  • Cardiovascular Biology
  • Molecular Pharmacology
  • Structural Biology

Background:

  • Cardiac disease is a leading global cause of death.
  • The β1-adrenergic receptor (β1-AR) regulates cardiac function but is downregulated in heart failure.
  • β1-AR activation of Gs proteins increases heart rate and contractility.

Purpose of the Study:

  • To investigate the molecular mechanism of β1-AR-mediated Gs protein activation.
  • To elucidate the structural changes involved in receptor-G protein coupling.

Main Methods:

  • Cryo-electron microscopy
  • Functional assays
  • Biochemical studies

Main Results:

  • Identified key conformational changes in Gs protein upon β1-AR binding.
  • Observed disruption of hydrogen bonds and interacting networks, including His373 and Gln59.
  • These changes likely deform the GDP-binding pocket of Gs protein.

Conclusions:

  • Provided molecular insights into the activation mechanism of Gs protein by β1-AR.
  • Elucidated structural basis for G-protein-coupled receptor signaling.
  • Findings may contribute to understanding and treating heart failure.

Keywords:
G-proteinG-protein-coupled receptoractivation of G-proteinscardiac diseasecryo-electron microscopysignal transductionstructural biologyβ1-adrenergic receptor

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